Wilms tumor gene 1 (WT1), TP53, RAS/BRAF and KIT aberrations in testicular germ cell tumors.

PURPOSE: Wilms tumor gene 1 (WT1), a zinc-finger transcription factor essential for testis development and function, along with other genes, was investigated for their role in the pathogenesis of testicular germ cell tumors (TGCT). METHODS: In total, 284 TGCT and 100 control samples were investigated, including qPCR for WT1 expression and BRAF mutation, p53 immunohistochemistry detection, and massively parallel amplicon sequencing. RESULTS: WT1 was significantly (p < 0.0001) under-expressed in TGCT, with an increased ratio of exon 5-lacking isoforms, reaching low levels in chemo-naïve relapsed TGCT patients vs. high levels in chemotherapy-pretreated relapsed patients. BRAF V600E mutation was identified in 1% of patients only. p53 protein was lowly expressed in TGCT metastases compared to the matched primary tumors. Of 9 selected TGCT-linked genes, RAS/BRAF and WT1 mutations were frequent while significant TP53 and KIT variants were not detected (p = 0.0003). CONCLUSIONS: WT1 has been identified as a novel factor involved in TGCT pathogenesis, with a potential prognostic impact. Distinct biologic nature of the two types of relapses occurring in TGCT has been demonstrated. Differential mutation rate of the key TGCT-related genes has been documented.

Estimating cancer incidence, prevalence, and the number of cancer patients treated with antitumor therapy in 2015 and 2020 -  analysis of the Czech National Cancer Registry.

BACKGROUND: Cancer burden in the Czech population ranks among the highest worldwide, which introduces a strong need for a prospective modelling of cancer incidence and prevalence rates. Moreover, a prediction of number of cancer patients requiring active antitumor therapy is also an important issue. This paper presents the stage-specific predictions of cancer incidence and prevalence, and the stage- and region-specific patients requiring active antitumor therapy for the most common cancer diagnoses in the Czech Republic for years 2015 and 2020. The stage-specific estimates are also presented with regard to the treatment phase as newly diagnosed patients, patients treated for non-terminal recurrence, and patients treated for terminal recurrence. PATIENTS AND METHODS: Data of the Czech National Cancer Registry from 1977 to 2011 has been used for the analysis, omitting the records of patients diagnosed as death certificate only or at autopsy. In total, 1,777,775 incidences have been considered for the estimation using a statistical model utilizing solely the population-based cancer registry data. All estimates have been calculated with respect to the changing demographic structure of the Czech population and the clinical stage at diagnosis. RESULTS: Considering year 2011 as the baseline, we predict 89%, 15%, 31% and 32% increase in prostate, colorectal, female breast and lung cancer incidence, respectively, in 2020 resulting in 13,153, 9,368, 8,695, and 8,604 newly dia-g--nosed cancer patients in that year, respectively. Regarding cancer prevalence in 2020, the estimated increase is 140%, 40%, 51%, and 17% for prostate, colorectal, female breast and lung cancer, respectively, meaning that more than 100,000 prevalent female breast cancer patients as well as more than 100,000 prevalent prostate cancer patients are expected in the Czech Republic. The estimated numbers of patients requiring active antitumor therapy for prostate, colorectal, female breast and lung cancer in the Czech Republic in 2020 are 23,652, 14,006, 14,759 and 8,272; respectively. CONCLUSIONS: The analysis documents a serious increase in cancer incidence and prevalence in the Czech Republic in years 2015 and 2020 when compared to the situation in 2011. Regarding the estimated numbers of patients requiring active antitumor therapy, the model confirms a continuous increase that must be accounted for in the future planning of health care in the Czech Republic.

[Epidemiology of screening-targeted cancers according to new data of the Czech National Cancer Registry]. / Epidemiologie zhoubných nádoru cílených screeningem dle nových dat Národního onkologického registru Ceské republiky.

The Czech Society for Oncology has developed an information system which combines the population-based Czech National Cancer Registry with clinical databases in order to cover the main areas of health care assessment - monitoring of the population burden, prediction of the number of cancer patients, diagnostic and treatment results. The presented data demonstrate a high cancer burden within the Czech population - each year there are approximately 8,000 new cases of colorectal cancer, 6,500 new cases of breast cancer, and 1,000 new cases of cervical cancer. And each year, about 4,000 people die from colorectal cancer, around 2,000 women die from breast cancer, and approximately 400 women die from cervical cancer in the Czech Republic. Population-based screening programmes focus on all of the above-mentioned groups of malignant tumours; therefore, it is essential to monitor epidemiological trends in order to assess the screening impact. Despite the high incidence rates of all three cancer types, the trend in mortality rates has been stable or has even decreased in the long term, which has inevitably led to a significant increase in the total prevalence of cancer patients. In 2011, the prevalence of colorectal cancer, breast cancer and cervical cancer amounted to 51,064 people, 67,261 women and 17,398 women, respectively. When compared with the year 2001, there was a 59%, 69% and 25% increase in the prevalence of colorectal cancer, breast cancer, and cervical cancer, respectively. Undoubtedly, taking care of high numbers of cancer patients will continue to require significant financial resources in the near future. As the epidemiological burden is still on the increase, preventive programmes need to be further promoted, including secondary prevention, which is provided through organised screening programmes. Although effective methods exist for timely diagnosis of all three of the above-mentioned cancer types, the epidemiological situation in the Czech Republic is being steadily worsened by a relatively high proportion of primary cancers being diagnosed too late. Each year, more than 50% of new colorectal cancer cases are diagnosed in clinical stage III or higher; in cervical cancer, this proportion is nearly 35%. By contrast, the well-promoted breast cancer screening programme has led to more than 75% of new cases of breast cancer being diagnosed in stages I or II, when the chance of successful treatment is significantly higher.

Cancer incidence and mortality in the Czech Republic.

BACKGROUND: The Czech Republic ranks among the countries with the highest cancer burden in Europe as well as worldwide. The purpose of this study is to summarize longterm trends in the cancer burden and to provide up-to-date estimates of incidence and mortality rates after 2011. DATA AND METHODS: The Czech National Cancer Registry (CNCR) was instituted in 1977 and contains information collected over a 34-year period of standardized registration covering 100% of cancer diagnoses within the entire Czech population. The CNCR analysis is supported by demographic data and by the Death Records Database. An overview of the epidemiology of malignant tumors in the Czech population is available online at www.svod.cz. RESULTS: All neoplasms, including nonmelanoma skin cancer, reached a crude incidence rate of almost 802 cases per 100,000 men and 681 cases per 100,000 women in 2011. The annual mortality rate exceeded 258 deaths per 100,000 individuals; in other words, more than 27,000 individuals die of cancer each year. The overall incidence of malignancies has increased with a growth index of +27.6% during the last decade (2001- 2011), while the mortality rate has been stabilized over the time span (growth index in 2001- 2011: - 5.0%). Consequently, the prevalence has significantly increased in the observed period and exceeded 475,000 cases in 2011. In addition to demographic aging of the Czech population, the cancer burden has also increased due to the growing incidence of multiple primary tumors (recently more than 15% of the total incidence). The most frequent diagnoses include colorectal cancer, lung cancer, breast cancer, and prostate cancer. Although some neoplasms are increasingly diagnosed at an early stage (e. g. the proportion of stage I or II was 75.3% for female breast cancer and 84.2% for skin melanoma), the numbers of early diagnosed cases are generally insufficient, even in the case of highly prevalent cancers such as colorectal carcinoma (only 46.1% of incident cases are diagnosed at stage I or II, according to recent data). CONCLUSION: Population-based data on malignant tumors are available in the Czech Republic. The data survey can help us define national cancer management priorities. The current priority is to achieve a sustained reduction of cases diagnosed at an advanced stage and reduction of the significant regional differences in diagnostic efficiency.

[Cost analysis of radiotherapy provided in inpatient setting -  testing potential predictors for a new prospective payment system]. / Analýza nákladu na radioterapii v luzkové péci - hledání vhodných prediktoru pro potreby nového prospektivního úhradového modelu.

BACKGROUND: As a part of the development of a new prospective payment model for radiotherapy we analyzed data on costs of care provided by three comprehensive cancer centers in the Czech Republic. Our aim was to find a combination of variables (predictors) which could be used to sort hospitalization cases into groups according to their costs, with each group having the same reimbursement rate. We tested four variables as possible predictors -  number of fractions, stage of disease, radiotherapy technique and diagnostic group. METHODS: We analyzed 7,440 hospitalization cases treated in three comprehensive cancer centers from 2007 to 2011. We acquired data from the I COP database developed by Institute of Biostatistics and Analyses of Masaryk University in cooperation with oncology centers that contains records from the National Oncological Registry along with data supplied by healthcare providers to insurance companies for the purpose of retrospective reimbursement. RESULTS: When comparing the four variables mentioned above we found that number of fractions and radiotherapy technique were much stronger predictors than the other two variables. Stage of disease did not prove to be a relevant indicator of cost distinction. There were significant differences in costs among diagnostic groups but these were mostly driven by the technique of radiotherapy and the number of fractions. Within the diagnostic groups, the distribution of costs was too heterogeneous for the purpose of the new payment model. CONCLUSION: The combination of number of fractions and radiotherapy technique appears to be the most appropriate cost predictors to be involved in the prospective payment model proposal. Further analysis is planned to test the predictive value of intention of radiotherapy in order to determine differences in costs between palliative and curative treatment.

[On the importance of standardization in the assessment of population-based cancer patient survival in the Czech Republic -  methodology and results from the Czech National Cancer Registry]. / Význam standardizace v hodnocení populacního prezití onkologických pacientu v CR -  metodický koncept a výsledky analýzy dat Národního onkologického registru.

BACKGROUND: Calculating 5-year overall and relative survival is the standard method for population-based analyses in oncology. Survival rates based on population data do not, however, guarantee standardized benchmarks for comparison of different patient populations, which is especially true when compared populations differ considerably in age structure and representation of clinical stages. In this paper, we present and compare statistical methods for standardization of cancer survival rates. PATIENTS AND METHODS: Using data of the Czech National Cancer Registry, we estimated 5-year overall and relative survival estimates for periods 2001- 2005 and 2006- 2010. To demonstrate the effect of standardization, we calculated crude and age -standardized survival rates as well as survival rates standardized for both age and clinical stage. RESULTS: Our results show that the particular standardization method influences resulting 5-year overall and relative survival rates regarding both within and between time periods comparisons. In addition, our results document a recent improvement in 5-year relative survival between periods 2001- 2005 and 2006- 2010 for 19 of 20 evaluated diagnoses. All most prevalent cancers including prostate, lung, colorectal, breast, kidney, and uterine cancer and melanoma were observed among the diagnoses with statistically significantly improved patient survival. CONCLUSION: Unless the use of standardization to the age and stage of tumor is limited due to a small number of patients in individual age-  and stage- specific subgroups, this method can be considered as a proper statistical methodology for the population assessment of Czech cancer patient survival rates.

Positron emission tomography and clinical predictors of survival in primary extragonadal germ cell tumors.

BACKGROUND: Primary extragonadal germ cell tumors (EGTs) are an uncommon malignancy -accounting for 2-4% of all germ cell neoplasms in adult males. Their prognosis is worse than that for testicular germ cell tumors because of their relative chemoresistance and frequent presentation with widely disseminated metastases. We have studied the role of fluorodeoxyglucose positron emission tomography (FDG-PET) for outcome prediction of patients with EGTs. PATIENTS AND METHODS: We have retrospectively analysed 36 men with germ cell tumors originating in the mediastinum or the retroperitoneum. All patients were treated between 1994 and 2010. Negative result of testicular ultrasonographic examination and/or testicular biopsy was required for diagnosis of EGT. Platinum-based systemic therapy was used in all cases, and resectable residual tumor masses were removed surgically. RESULTS: Overall survival at one and three years was 81% (95% confidence interval [CI]: 68-94%) and 55% (CI: 38-71%), respectively. None of the patients who had positive FDG-PET findings after first line chemotherapy survived at three years after diagnosis. In contrast, 69% and 20% of patients with positive tumor markers, and 90% and 67% of patients with negative tumor markers after first line chemotherapy survived at one and three years, respectively. Negative FDG-PET after completion of treatment was also a powerful predictor of long-term survival with 100% patients surviving three years and 89% surviving five years after diagnosis. CONCLUSIONS: Negative FDG-PET after first-line chemotherapy or after the completion of systemic treatment and resection of residual tumor masses strongly predicts long-term event-free survival in patients with EGTs.

Skin toxicity and efficacy of sunitinib and sorafenib in metastatic renal cell carcinoma: a national registry-based study.

BACKGROUND: A retrospective, registry-based analysis to assess the outcomes of metastatic renal cell cancer (mRCC) patients treated with sunitinib and sorafenib who developed dermatologic adverse events was performed. PATIENTS AND METHODS: Data on mRCC patients treated with sunitinib or sorafenib were obtained from the Czech Clinical Registry of Renal Cell Cancer Patients. Outcomes of patients who developed hand-foot syndrome (HFS) of any grade and/or grade 3/4 rash during the treatment were compared with patients without HFS and no, mild, or moderate rash. RESULTS: The cohort included 705 patients treated with sunitinib and 365 patients treated with sorafenib. For sunitinib, the median overall survival (OS) was 43.0 months versus 31.0 months (P = 0.027) and median progression-free survival (PFS) 20.8 months versus 11.1 months (P = 0.007) for patients with versus without dermatologic toxicity, respectively. For sorafenib, the median OS and PFS were 27.9 and 24.6 months (P = 0.244), and 12.2 and 8.8 months (P = 0.050), respectively. In multivariable Cox regression, the skin toxicity was significantly associated with longer OS in the sunitinib cohort. CONCLUSION: The presence of skin toxicity is associated with improved OS and PFS in patients with mRCC treated with sunitinib.

Sunitinib followed by sorafenib or vice versa for metastatic renal cell carcinoma--data from the Czech registry.

BACKGROUND: Sequential therapy with tyrosine kinase inhibitors (TKIs), sunitinib and sorafenib, is a common treatment choice for patients with advanced/metastatic renal cell carcinoma (mRCC) despite lack of randomised trials. The aim of this retrospective registry-based study was to analyse the outcomes of RCC patients treated with sunitinib-sorafenib or sorafenib-sunitinib sequence. PATIENTS AND METHODS: The Czech database containing information on patients treated for mRCC using targeted agents was used as a source of data for retrospective analysis. There were 138 patients treated with sunitinib-sorafenib sequence and 122 patients treated with sorafenib-sunitinib sequence. RESULTS: Progression-free survival (PFS) was 17.7 months for patients treated with sunitinib-sorafenib sequence and 18.8 months for those receiving sorafenib followed by sunitinib (P = 0.47). Overall survival (OS) at 1 year was 83% [95% confidence interval (CI) 77% to 90%] for patients treated with sunitinib-sorafenib and 84% (95% CI 77% to 91%) for sorafenib-sunitinib patients (P = 0.99). Treatment toxic effects were predictable but a significant proportion of patients (up to 14%-25% for different lines of therapy and used TKI) switched between TKIs or discontinued TKI therapy because of toxicity. CONCLUSIONS: In contrast to most of the previously published reports, we have not observed improved PFS or OS for mRCC patients treated with the sorafenib-sunitinib sequence as compared to the sunitinib-sorafenib sequence.

[Cost analysis of XELOX and FOLFOX-4 chemotherapy regimens for colorectal carcinoma]. / Porovnání nákladu u rezimu XELOX a FOLFOX-4 v lécbe kolorektálního karcinomu.

BACKGROUND: The aim of our study was to compare healthcare-related costs of treatment with XELOX and FOLFOX4 chemotherapeutic regimens in patients with colorectal cancer. We have evaluated costs claimed to the health insurance by the hospital administering these cancer therapies. This study is a pilot project utilising the new I-COP database developed by the Institute of Biostatistics and Analyses of the Masaryk University in Brno, Czech Republic. PATIENTS AND METHODS: First, we estimated the costs based on current prices of procedures, medication, and materials from public sources. Using the I-COP database, we then carried out a matched-pair comparison of 26 patients treated with FOLFOX4 or XELOX for colorectal cancer. We evaluated a period of three months of therapy (i.e. 6 cycles of FOLFOX4 or 4 cycles of XELOX). Statistical analysis was done using the Wilcoxon matched pairs test. RESULTS: The estimated cost for three months of therapy was 148,288 Czech crowns (CZK) for FOLFOX4 (including CZK 101,064 for chemotherapy drugs) and CZK 123,756 for XELOX. The overall costs claimed to the insurance companies were CZK 160,158 and CZK 151,176 for FOLFOX4 and XELOX, respectively (p = 0.221). The XELOX regimen had significantly higher costs for chemotherapy drugs (CZK 131,705 versus 114,531, p = 0.023) whereas other costs were lower than those for FOLFOX4. CONCLUSIONS: FOLFOX4 and XELOX regimens can be considered as equivalent in terms of costs claimed by the hospital administering cancer treatment.

[Metastatic renal cell carcinoma treated with everolimus--data from the RENIS Clinical Registry]. / Výsledky terapie metastatického renálního karcinomu lékem everolimus--analýza udaju z klinického registru RENIS.

Everolimus is an oral mTOR kinase inhibitor approved for the treatment of patients with metastatic renal cell carcinoma (mRCC) progressing during or after treatment with vascular endothelial growth factor (VEGF)-targeted agents. Using the national RENIS clinical registry, we have retrospectively analysed outcomes of patients treated for mRCC with everolimus. A total of 78 patients were evaluable. Median progression-free survival from the start of everolimus therapy was 7 months (95% confidence interval 2-12 months). Partial response or stable disease was achieved in 69% of patients. Treatment toxicity was predictable and serious adverse events occurred in only 6% of patients the most common being respiratory toxicity. Everolimus therapy provides significant clinical benefit for heavily pretreated mRCC patients after failure of VEGF-targeted therapy.

[Positron emission tomography in the diagnosis and monitoring of patients with nonseminomatous germ cell tumours]. / Pozitronová emisní tomografie v diagnostice a sledování pacientu s neseminomovými germinálními nádory.

The role of 18-fluorodeoxyglucose positron emission tomography (FDG-PET) in the diagnosis and monitoring of nonseminomatous germ cell tumours is currently unclear. Clinical studies have suggested that FDG-PET has relatively low sensitivity and specificity in the setting of initial staging and viability assessment of post-chemotherapy residual lesions. On the other hand, FDG-PET provides potentially useful information in patients with elevated tumour markers and/or multiple residual lesions with limited resectability. Other possible indications of FDG-PET are the early assessment of tumour chemosensitivity and the diagnosis of inflammatory treatment complications.

Cancer incidence and mortality in the Czech Republic.

BACKGROUNDS: The Czech Republic is ranked among those countries with the highest cancer burden in Europe and worldwide. The purpose of this study is to summarize long-term trends in the cancer burden and to provide up-to-date estimates of incidence and mortality rates from 2007. MATERIAL AND METHODS: The Czech National Cancer Registry (CNCR) was instituted in 1977 and contains information over a 30-year period of standardized registration covering 100% of cancer diagnoses and the entire Czech population. The analysis of CNCR is supported by demographic data of the Czech Republic and by the Death Records Database as civil registration systems. The epidemiology of malignant tumours in the Czech population is available online at www.svod.cz. RESULTS: All neoplasms, including non-melanoma skin cancer, reached a crude incidence rate of almost 736 cases per 100,000 men and 648 cases per 100,000 women in 2007. The annual mortality rate exceeded 263 deaths per 100,000 population; each year, more than 27,000 persons die of cancer. The overall incidence of malignancies has increased during the last decade with growth index + 26.4% (1997-2007) while the mortality rate has stabilized over this time span (growth index in 1977-2007: -2.5%). Consequently, the prevalence has significantly increased in the registration period and in 2007 it exceeded 400,000 cases. In addition to the demographic ageing of the Czech population, the cancer burden is increased by the growing incidence of multiple primary tumours (recently more than 11% of the total incidence). The most frequent diagnoses include colorectal cancer, lung cancer, breast cancer and prostate cancer. Although some neoplasms are increasingly diagnosed at an early stage (e.g. proportion of stage I + II in female breast cancer: 71.9%, skin melanoma: 81.3%), in general early diagnostics is insufficient in the Czech Republic. This is the case even for highly prevalent colorectal carcinoma (only 43.2% of incident cases recently diagnosed at stage I or II). CONCLUSION: The Czech Republic is well equipped with high-quality and functional facilities for collecting and analysing population-based data on malignant tumours. The data survey has enabled the priorities of cancer management in the Czech Republic to be defined. This will undoubtedly lead to a sustained reduction in late diagnosed cases and a reduction in the remarkable regional differences in diagnostic efficiency.

[Malignant subtype of cystosarcoma phyllodes with brain metastases]. / Maligní forma cystosarcoma phyllodes s metastázami do mozku.

Cystosarcoma phyllodes is an uncommon type of breast tumour. Benign, borderline, and malignant subtypes have been described. Central nervous system metastases of the malignant subtype of cystosarcoma phyllodes are rare and associated with poor prognosis. We report on a patient with malignant cystosarcoma phyllodes who developed metastatic disease six years after resection of the primary breast tumour. Partial regression of a brain metastasis was achieved using radiotherapy but the patient later died due to widespread metastatic disease which was uncontrollable by systemic chemotherapy. Because metastatic malignant cystosarcoma phyllodes are largely resistant to treatment, the most important objective is to provide optimal management of the primary tumour before dissemination occurs.

[Influenza vaccination for adult patients with solid malignancies]. / Vakcinace proti chripce u dospelých pacientu se solidními nádory.

Seasonal influenza causes annual epidemics with significant morbidity in the general population and important mortality in high-risk groups. Opinions on the suitability of patients with solid tumours in different phases of antineoplastic therapy to receive influenza vaccination vary considerably among oncologists, sometimes even within one center. Consequently, a large number of cancer patients fail to receive influenza vaccination. Recently, the situation has become even more complicated due to the emergence of the new pandemic A/H1N1 ("swine" or "Mexican") influenza. We review current knowledge on the epidemiology of influenza, vaccination recommendations, and the efficacy and toxicity of available influenza vaccines in the population of adult patients with solid malignancies.

[Therapeutic approaches for early stage nonseminomatous germ cell testicular tumors]. / Lécebné postupy u nepokrocilých testikulárních germinálních nádoru neseminomového typu.

The author deales with current therapeutical approaches for early stage nonseminomatous germ cell testicular tumours, including preinvasive stage CIS (carcinoma in situ). All presented recommendation results from "European Association of Urology Guidelines-2007" and are based on respected risk factors of the disease progression. When all recommended approaches are kept, then most of these patients are fully curable (<95).

Multivariate analysis of risk factors for testicular cancer: a hospital-based case-control study in the Czech Republic.

Growing incidence of testicular cancer around the world stimulates research attempting to explain the trends. This study quantified the contribution of different types of potential risk factors for testicular germ-cell cancer (TGCC) with differentiation between seminoma and non-seminoma. A standardized questionnaire containing demographic data, pre- and perinatal factors, social, lifestyle and occupational parameters was prepared. The data file consists of n = 356 TGCCs (seminoma: n = 195; non-seminoma: n = 161) and n = 317 controls, frequency matched on age to cases. The following factors were significantly associated with the risk of TGCCs in univariate analyses (ORs): atrophic testis (5.3), smoking over 12 pack-yr (4.9), cryptorchidism (2.9), testicular trauma (2.0), birth weight under 3,000 g (1.6), low degree of education (3.0) in correlation with manual occupation (2.3) and finally, overall familial cancer history (1.5) and familial history of breast (1.8) and prostate cancer (3.9). On the other hand, maternal age over 20 yr (OR < 0.4) and moderate recreational sport activity (OR = 0.5) significantly reduced the risk of TGCCs. A significant risk was associated with cryptorchidism (OR = 2.9; 95% CI = 1.5 - 5.9) where orchidopexy was delayed after 5 yr of age (OR = 5.2; 95% CI = 1.5-18.1). Delayed orchidopexy was associated namely with the risk of seminomas (OR = 7.5; 95% CI = 2.1-26.7). Only some of the variables were retained in multivariate model for TGCCs as well as for histological subtypes (multivariate adjusted OR for all TGCCs): atrophic testis (5.9), family history of prostate cancer (4.8), cryptorchidism (3.8) and interaction term 'low degree of education & manual occupation' (3.0). Familial history of breast cancer elevated risk of TGCCs and of seminomas (OR: 2.01 - 2.18). Birth weight under 3,000 g was retained in a multivariate model for TGCCs with a borderline significance (OR = 1.67). We could not rule out any type of risk factors, as each one was significantly represented in the final multivariate models. Familial cancer history remained to be an influential risk factor, altogether with some lifestyle and occupational parameters. This suggests that both environmental exposures and genetic inheritance can play role in the moderation of the risk of TGCC.

Vinorelbine, epirubicin, and methotrexate (VEM) as primary treatment in locally advanced breast cancer.

PURPOSE: This phase II trial of VEM (vinorelbine + epirubicine + methotrexate) in the treatment of locally advanced breast cancer was conducted to obtain downstaging to allow surgery and breast conservation. PATIENTS AND METHODS: This multicenter study recruited 58 patients with locally advanced breast cancer (two patients ineligible); 56 were evaluable for response and tolerance. RESULTS: Downstaging was obtained in 77% of the patients with a pathological complete response (pCR) rate of 9%. At 33 months of follow-up, median survival has not been reached. Neutropenia grade 3-4 was reported in 31% of cycles with 3% of cycles with infection grade 3. Alopecia grade 3 was noticed for 71% of patients. CONCLUSION: VEM represents an effective regimen for patients with locally advanced breast cancer, allowing an important pCR. Moreover, this regimen appears to be particularly well tolerated.

[Possibilities of curative chemotherapy of solid tumours]. / Moznosti kurativní chemoterapie solidních nádoru.

The author analyzes the terms "cure", "curability" in relation to solid tumours at different sites. The attitude to so-called cure changed with time as the therapeutic possibilities changed. At the same time various markers, prognostic and predictive factors (epidemiological, anatomical and cellular and molecular genetic), were sought and found. On an international scale the extent of the disease was defined more accurately and codified and this was reflected in the TNM system. The attitude to such biological phenomena as spontaneous remission or late metastases changed also. A quite new clinical meaning was acquired by the phenomenon described histopathologically as maturation. In the sixties for the first time complete remission of a disseminated testicular tumour was described after combined chemotherapy and complete remission of a disseminated gestational choriocarcinoma. At the same time reports were published on successful treatment of Wilms tumour of the kidneys. Germinal testicular tumours have become since the middle of the eighties (i.e. the period when routine use of cisplatinum started) the model of a "curable" tumour of adult age. With the introduction of adjuvant and neoadjuvant chemotherapy five-year survivals improve and thus also the prognosis of breast cancer. Empirically the number of years which elapsed after termination of treatment of different tumours and which are already "safe" and there is nofurther risk of a relapse of the original disease. However in the course of years which have elapsed since the platinum boom late post-therapeutic changes develop and late relapses (after more than 10 years) in cured originally generalized testicular tumours. The term "cure" has no doubt its limitations and applies only in relation to the sum of biological characteristics of a certain tumour.